In the brains of patients with Alzheimer's disease, peptides each consisting of approximately 40 amino acids, called amyloid-β proteins, which widely accumulate outside neurons to form insoluble plaques (senile plaques) are observed. These senile plaques are thought to kill neurons and cause the onset of Alzheimer's disease. As therapeutic agents for Alzheimer's disease, agents promoting degradation of amyloid-β proteins and amyloid-β vaccines have been studied.
Secretases are enzymes which cleave a protein called amyloid-β precursor protein (APP) within a cell and generate an amyloid-β protein. An enzyme which produces N-terminals of amyloid-β proteins is called as BACE1 (beta-site APP-cleaving enzyme 1, β-secretase). It is considered that production of amyloid-β proteins may be suppressed by inhibiting this enzyme, and thus a substance with such an effect can serve as a therapeutic agent for Alzheimer's disease.
Non-Patent Document 1 discloses a 2-aminopyrimidin-4-one derivative which has a structure similar to that of the compound of the present invention. However, the document only discloses that this substance is useful as an antitumor drug.
Further, 2-aminopyrimidin-4-one derivatives in Patent Documents 1 to 7 and Non-Patent Document 2, 2-aminopyridine derivatives in Patent Document 8 and Non-Patent Document 3, and an aminodihydrothiazine derivative in Patent Document 9 are known as BACE1 inhibitors. However, each of these substances has a structure different from that of the compound of the present invention.
Patent Document 1: WO 2006/041404
Patent Document 2: WO 2006/041405
Patent Document 3: WO 2005/058311
Patent Document 4: WO 2006/065277
Patent Document 5: WO 2007/058580
Patent Document 6: WO 2007/146225
Patent Document 7: WO 2007/114771
Patent Document 8: WO 2006/065204
Patent Document 9: WO 2007/049532                Non-Patent Document 1: Journal of Medicinal Chemistry, 1995, 38, 1493-1504        Non-Patent Document 2: Journal of Medicinal Chemistry, 2007, 50, 5912-5925        Non-Patent Document 3: Journal of Medicinal Chemistry, 2007, 50, 1124-1132        